The overall goal of this project is to improve the results of treatment for tendon injury through a better understanding of, and the development of therapies that affect the tendon gliding surface. The underlying hypothesis continues to be that improvements in the results of flexor tendon repair can be obtained by methods that minimize friction of the gliding surfaces of tendon and sheath. Changes in suture methods and postoperative therapy regimens have improved the results of tendon repair and rehabilitation, but adhesions still occur. We therefore plan to study methods to further improve gliding and reduce adhesions by physicochemical and pharmacological modification of the tendon gliding surface, and the effect of these modifications on tendon healing, tendon gliding, and the expression of natural lubricants on the tendon surface, principally hyaluronan and lubricin. Our Specific Aims are, first, to investigate the effect of physicochemical attachment of hyaluronan and lubricin to the tendon surface on tendon gliding in canine and human tendons in vitro; second, to investigate the effects of physicochemical attachment of lubricants to the tendon gliding surface on tendon healing and tendon gliding in a canine model in vivo; and, third, to investigate the effects of pharmacological tendon surface modification with topical 5 fluorouracil on tendon healing, tendon gliding, and the expression of tendon surface lubricants in a canine model in vivo. The specific hypotheses that will be tested are, respectively, that physicochemical attachment of lubricants to the tendon surface will enhance tendon gliding ability in vitro; that physicochemical attachment of lubricants to the healing tendon surface will enhance tendon gliding ability, reduce adhesions, and not adversely affect tendon healing; and that pharmacologic treatment of the healing tendon surface will be associated with an increase in surface lubricants and a reduction in gliding resistance, without adversely affecting tendon healing. Based on the results of the work proposed here, we anticipate future studies, which might directly manipulate the expression of these surface lubricants, with the ultimate aim of producing adhesion-free tendon gliding and a soundly healed tendon after tendon injury and repair.